c-til051 in non-small cell lung cancer

Conditions: Metastatic Non Small Cell Lung Cancer

Summary: the goal of this phase 1 clinical study is test tumor infiltrating lymphocytes (known as c-til051) with nktr-255 and anti-pd1 therapy for subjects with refractory non-small cell lung cancer. the purpose of this study is to: 1. test the safety and ability for subjects to tolerate the til therapy 2. measure to see how the nsclc responds to the til therapy participants will be asked to: * provide a tumor sample prior to the start of any treatment which will be used to make the c-til051. * receive standard of care treatment until their lung cancer no longer responds * when necessary, the c-til051 will be manufactured by the sponsor and sent back to the site * subject will then receive chemotherapy (called lymphodepletion) for 3 days followed by 2 days of rest * c-til051 will then be infused on day 0 followed by nktr-255 (il-15) about 12 to 24 hours later * pembrolizumab will be administered every 3 weeks for up to 2 years nktr-255 is a novel polymer-conjugated human il-15 receptor agonist molecule designed to increase the proliferation and survival of memory cd8+ t cells and enhance the formation of long-term immunological memory which may lead to sustained anti-cancer immune response. the combination of nktr 255 and til's could improve proliferation and persistence of cellular therapies leading to enhanced anti-tumor activity.


Eligibility criteria:
inclusion criteria: * able to understand and give written informed consent * histologically and cytologically confirmed diagnosis of stage iv or recurrent non-small cell lung cancer (nsclc) with adenocarcinoma or squamous histology * planned for treatment with an anti-pd1 agent * tumor accessible by surgery, previously not irradiated and ≥ 1.5 cm in diameter * measurable disease after resection of tumor by recist 1.1 * ecog ≤ 1 * expected survival \> 6 months * adequate organ and marrow function * echo, muga or cardiac stress test within past 6 months showing lvef \>50% and without evidence of reversible ischemia * pulmonary function tests within past 6 months showing dlco \>50% of predicted exclusion criteria: * previous treatment with pd1/pdl1 inhibitor for metastatic disease, immune checkpoint blockade (icb) given as part of definitive therapy for stage ib-iii disease with surgery or after chemo/radiation is acceptable if last dose of icb is at least 6 months prior to enrollment in this study. * known driver mutations such as egfr, alk, ros1, ret, metex14, and ntrk alterations. * current or prior use of any immunosuppressive medications within 14 days before tumor harvest * known active cns metastases which are symptomatic * history of leptomeningeal metastases * uncontrolled intercurrent illness * known history of hiv+ or aids, hepatitis c, acute or chronic active hepatitis b or other serious chronic infection * live vaccine within 30 days of tumor harvest * history of allogeneic organ transplant * history of primary immunodeficiency * hypersensitivity to anti-pd1 agent, cyclophosphamide, fludarabine, interleukin-2, gentamicin, or any excipient * any condition that may interfere with evaluation of study treatment, safety or study results * active infection that requires iv antibiotics within 7 days of tumor harvest * unresolved greater than grade 1 toxicity (ctcae v5.0) from previous therapy * history of interstitial pneumonitis of autoimmune etiology that is symptomatic or requires treatment * pulmonary disease history requiring escalating amounts of oxygen \> 2l * known autoimmune conditions requiring systemic immune suppression therapy other than low dose prednisone or equivalent. * other malignancy, other than cutaneous localized) that required active treatment in the last 2 years. * women who are pregnant or lactating * women of childbearing potential or fertile men who are unwilling to use effective contraception during study and 6 months after treatment